title: Inhibition of amyloid beta protein fibrillation by polymeric nanoparticles.
abstract: Copolymeric NiPAM:BAM nanoparticles of varying hydrophobicity were found to retard fibrillation of the Alzheimer's disease-associated amyloid beta protein (Abeta). We found that these nanoparticles affect mainly the nucleation step of Abeta fibrillation. The elongation step is largely unaffected by the particles, and once the Abeta is nucleated, the fibrillation process occurs with the same rate as in the absence of nanoparticles. The extension of the lag phase for fibrillation of Abeta is strongly dependent on both the amount and surface character of the nanoparticles. Surface plasmon resonance studies show that Abeta binds to the nanoparticles and provide rate and equilibrium constants for the interaction. Numerical analysis of the kinetic data for fibrillation suggests that binding of monomeric Abeta and prefibrillar oligomers to the nanoparticles prevents fibrillation. Moreover, we find that fibrillation of Abeta initiated in the absence of nanoparticles can be reversed by addition of nanoparticles up to a particular time point before mature fibrils appear.
authors.affiliation: Centre for BioNano Interactions, School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Celia
authors.initials: C
authors.lastname: Cabaleiro-Lago
authors.forename: Fiona
authors.initials: F
authors.lastname: Quinlan-Pluck
authors.forename: Iseult
authors.initials: I
authors.lastname: Lynch
authors.forename: Stina
authors.initials: S
authors.lastname: Lindman
authors.forename: Aedin M
authors.initials: AM
authors.lastname: Minogue
authors.forename: Eva
authors.initials: E
authors.lastname: Thulin
authors.forename: Dominic M
authors.initials: DM
authors.lastname: Walsh
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Dawson
authors.forename: Sara
authors.initials: S
authors.lastname: Linse
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D011108:Polymers / Q000737:chemistry*; D011485:Protein Binding; D020349:Surface Plasmon Resonance; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011108:Polymers; C078592:amyloid beta-protein (1-40)